Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART)

Journal of Translational Medicine

Sangeeta Lathkar-Pradhan¹  Thomas Crawford¹  Todd Koelling¹  Frank Bogun¹  Kirsta Bray¹  Le Kang²  Thomas Iden³  Alpha Berry Fowler³  Kelly Polly³  Aamer Syed³  Huzaefah Syed⁴  Lynda Rosenfeld⁵  David Birnie⁶  Melissa Smallfield⁷  Virginia Mihalick⁷  Kenneth Ellenbogen⁷  W. Gregory Hundley⁷  Shilpa Jasti⁷  Jordana Kron⁷  Emily Federmann⁷  Amy Ladd⁷  Jennifer H. Jordan⁸  Benjamin Van Tassell⁹  Antonio Abbate^1,10 

[1] Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA;Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA;Division of Pulmonary and Critical Care, Virginia Commonwealth University, Richmond, VA, USA;Division of Rheumatology, Virginia Commonwealth University, Allergy, and Immunology, Richmond, VA, USA;Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA;University of Ottawa Heart Institute, Ottawa, ON, Canada;VCU Pauley Heart Center, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, P.O. Box 980053, 23298-0053, Richmond, VA, USA;VCU Pauley Heart Center, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, P.O. Box 980053, 23298-0053, Richmond, VA, USA;Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA;VCU Pauley Heart Center, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, P.O. Box 980053, 23298-0053, Richmond, VA, USA;Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, USA;VCU Pauley Heart Center, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, P.O. Box 980053, 23298-0053, Richmond, VA, USA;Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA;

关键词: Cardiac sarcoidosis;    Interleukin-1;    Inflammation;    Heart failure;   

DOI  :  10.1186/s12967-021-03130-8

来源: Springer

【 摘 要 】

BackgroundSarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis.MethodsBuilding on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis.DiscussionThe current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities.Trial Registration The trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936.

【 授权许可】

CC BY